It is known in the prior art that the `ketoform synthesis` is highly effective in the synthesis of compounds which are otherwise difficult, if not impossible to synthesize. The `ketoform synthesis` is so called because a saturated or unsaturated monoketone ("ketone"), or, an aromatic monoaldehyde ("araldehyde"), and a haloform are reacted in the presence of a phase transfer catalyst, an organic solvent and aqueous or solid alkali, with a `starting` compound (referred to herein as the "reactant" compound), to yield various reaction products, the reaction being "base-induced". The structure of the reaction product depends upon the regioselectivity of the reaction with respect to particular portions of the structure of the reactant compound. Because the prior art ketoform synthesis was carried out in the presence of a phase transfer catalyst, it is referred to herein as the "catalytic ketoform synthesis".
It was hypothesized in the prior art reaction, that the presence of the phase transfer catalyst along with substantially equimolar quantities of ketone or aldehyde and haloform, was somehow responsible in this base-induced reaction, for avoiding side reactions which might form unwanted by-products such as isonitrile, formamide and alpha-chloro acids, inter alia. It has now been found that the formation of such unwanted byproducts is also avoided in the absence of the phase transfer catalyst, and a large excess of ketone, or araldehyde provided it (ketone/araldehyde) is a solvent for the reactant compound.
The catalytic ketoform synthesis is disclosed in U.S. Pat. Nos. 4,167,512; 4,297,497; and 4,298,737 to produce stabilizers for organic materials which are sensitive to ultraviolet light (referred to as u-v light stabilizers), and lubricity additives particularly in functional fluids. The disclosures of the foregoing patents are incorporated by reference thereto as if fully set forth herein. Briefly, either an acyclic or cyclic ketone, typically acetone, or an araldehyde, typically benzaldehyde (optionally substituted), and chloroform are each necessary reactants in the synthesis. In addition, at least one of them, that is, either the ketone/araldehyde or the haloform, is a solvent for the reactant compound, so that the ketone/araldehyde, the haloform and the solution of the reactant compound are all present in a nonaqueous phase. Also present is an aqueous phase and alkali, typically NaOH in solution.
For example, in U.S. Pat. No. 4,167,512 it was shown that polysubstituted 2-keto-1,4-diazacycloalkanes are easily synthesized from readily available starting materials, using the catalytic ketoform synthesis. Particularly, 1,2-diamines or 1,3-diamines are converted to the aforesaid polysubstituted cyclic compounds at room temperature and atmospheric pressure in the presence of an onium salt phase transfer catalyst.
U.S. Pat. No. 4,297,497 teaches the preparation of N.sup.1,N.sup.4 -dimethyl-3,3-dimethyl-2-piperazinone by the catalytic ketoform synthesis using N,N'-dimethyl-ethylene diamine as the reactant compound either with BTAC or a phosphonium salt.
U.S. Pat. No. 4,298,737 teaches the preparation of piperidinyl substituted 1,4-diaza-2-cycloalkanones by a catalytic ketoform synthesis in which the reactant compound is a N-piperidinyl substituted diamine such as 4-(3-amino-1,3-dimethyl-butylamino)-2,2,6,6-tetramethylpiperidine.
A more detailed discussion of the base-induced catalytic ketoform synthesis will be found in "Hindered Amines. Synthesis of Hindered Acyclic -Aminoacetamides" by Lai, John T., J. Org. Chem., 45, 3671-3 (1980). Despite the effectiveness of the phase transfer catalyst in the ketoform synthesis, the synthesis is burdened with the cost of separating and recovering the expensive phase transfer catalyst. Simply separating the catalyst from the reaction mass often presents more of a problem than is economically tolerable, with the result that otherwise highly useful and desirable compounds never find their way to the marketplace. Moreover, this catalytic ketoform synthesis was only known to be useful in the formation of cyclized reaction products; now it may be used for the formation of acyclic reaction products as well.
The logical approach to solve the problem was to devise several ways of trying to separate the catalyst from the reaction mass, and/or ways to confine the catalyst in the reaction zone so that separation and recovery of the catalyst would be a more manageable problem. Neither approach appreciably alleviated the economic burden of having to separate and recover the catalyst.
Quite by chance, it transpired that the most economical way to solve the problem of separating and recovering catalyst was to avoid using the catalyst in the first place. Thus, it is to this catalyst-free (hence termed "non-catalytic") ketoform synthesis, to which this invention is directed.
A long time ago, the influence of substituents in the C.sub.6 H.sub.6 nucleus on the formation of aromatic isonitriles by the Hoffmann reaction, was studied by the reaction of chloretone (formed by the reaction of chloroform with acetone), aniline and KOH (see "Action of Chloretone and KOH on Primary Aromatic Base" by Banti, G., Gazz. Chim. Ital., 59 819-24, 1929). In the presence of ethanol as a solvent, the reaction product was phenylaminoisobutyric acid anilide. However, it has been found that presence of an alcohol solvent interferes with the directivity of the ketoform synthesis and tends to produce unwanted byproducts in my process, presumably because of the presence of free chloroform and a large excess of ketone. In my ketoform synthesis, if a primary alcohol is present, it is necessarily a reactant.
The problems with directivity and formation of byproducts are also thought to derive from the preformation of chloretone which may interfere with the formation of the trichloromethide ion. This trichloromethide ion is deemed essential to the formation of an epoxide intermediate in the ketoform synthesis. (see Lai, J. T. publication, supra). Formation of the epoxide intermediate is thought to occur in a manner analogous to that taught in an article titled "Formation of Dichloro Oxiranes from Ketones under Phase Transfer Conditions" by Greuter, H. et al., in Helvetica Chimica Acta, Vol 62 pg 1275-81 Fasc. 4 (1979)-Nr. 131. Thus, the non-catalytic ketoform synthesis of my invention is carried out without the preformation of chloretone and in the absence of alcohol.